Why genes hold the clue to curing sepsis

"It's hard sometimes not to dwell on thinking that it could have been worse," said Mrs King, speaking ahead of World Sepsis Day on Tuesday.

"We're one of the lucky ones."

Aimee King and son, Corey, who recovered from a life-threatening bout of sepsis last Christmas (Image: Sepsis Research FEAT)

Corey survived and is now back to full health, but the condition is known to claim at least 4000 lives a year in Scotland.

Exactly why sepsis happens - and why some people are more susceptible to it than others - remains a mystery, but it is a puzzle that scientists in Edinburgh are working to unlock.

Sepsis - sometimes known as septicaemia or blood poisoning - is characterised by a major malfunction of the immune response to an infection, which results in it attacking the patient's own organs. It can be triggered by both viral or bacterial infections.

Although symptoms can be vague and hard to spot, key signs in younger children include difficulty breathing, a rash that doesn't fade when a glass is rolled over it, being sleepier than normal, and blue, pale or blotchy skin, lips or tongue.

In older children and adults, confusion or slurred speech can also be a warning sign, while very high or low temperatures, redness and swelling around a wound, vomiting, and a lack of urination should also ring alarm bells.

The leading theory is that some people are genetically predisposed to these abnormal reactions to infection, although precisely which genes and mutations are behind it is still being unravelled.

"Your chances of developing sepsis if a first-degree relative has had sepsis or died from sepsis is very high," said Dr Catharina Hartman, an Aberdeen-based emergency medicine consultant and trustee for the charity, Sepsis Research FEAT, which is helping to fund GenOMICC - a major study led by Edinburgh University which is analysing the DNA from patients who have become critically ill.

She added: "It's a bit like cancer, where some families have a high susceptibility to certain cancers. The same thing happens with sepsis so the answer must be somewhere in our genome - in that the way you respond to certain infection is determined by your genetic make up."

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In Corey's case, doctors believe that bacterial infections caused by streptococcus A and B had led to his sepsis - even though he experienced no obvious symptoms of the infections.

His mother became alarmed on December 27 when his skin became "really pale and grey, and his temperature was sky high".

He also had diarrhoea and had stopped eating.

She rushed him to A&E where doctors started Corey on antibiotics, but by the evening of December 28 the lymph nodes on his neck had become swollen and he was shivering uncontrollably.

"That's when I noticed the rash on his hands - he had this mottled look on his hands, and he just kept crying. It sounded like a 'help me' cry," said Mrs King.

"It hit me that Corey was dying. The sepsis had completely taken control of his body at this point."

Corey during his fight against sepsis (Image: xx)

On December 29, Corey was underwent emergency blood and platelet transfusions and doctors placed him into an induced coma to give his body a rest.

"It was touch and go," said Mrs King, a mother-of-eight.

"His blood pressure was really hard to stabilise - it was still too low. It was his lungs and his heart that were struggling with the sepsis."

By day 14, however, Corey was well enough to leave intensive care and was finally discharged home after nearly four weeks in hospital.

Corey King in recovery from sepsis (Image: Sepsis Research FEAT)

He is among the sepsis patients whose blood has been donated to GenOMICC Acute - a pilot study within GenOMICC which is specifically geared to understanding how DNA affects the immune response.

Professor Kenneth Baillie, a critical care consultant and chief investigator for GenOMICC, said: "In the larger GenOMICC study, the one that we've been running for the last seven years, we're just looking at DNA. So that’s pretty much static code that has existed in your body since you were conceived and encodes everything necessary to create a functioning human. The DNA code does that by sending molecular signals and different messages around individual cells in your body.

"In GenOMICC Acute, our pilot study, what we're doing is looking at some of those signals to look deeper into the mechanisms at a molecular level by which genetic changes influence the function of the immune system. So that means we're getting samples from patients shortly after their arrival in the intensive care unit."

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Scientists will seek to identify specific genetic mutations common to all or most sepsis patients, and then match that with drugs - some of which may already be available - which can target this particular area in order to reverse an abnormal immune response.

Dr Hartmann said: "We're looking at what exactly happens to the genes in those patients who get so sick. Once we understand what happens when people get so sick from sepsis, we can start to figure out what we need to do - what's the treatment we need to find, and where does it have to work on the genome to treat sepsis."

In the meantime, however, she noted that one of the biggest concerns around sepsis for those currently on the frontline are the delays in patients accessing care due to overcrowded A&E departments and ambulances unable to respond to 999 calls because they are stuck outside emergency departments, waiting to offload patients.

Dr Hartman said: "It's a worry for any time-critical illness - whether that's a heart attack, stroke, or anything, like sepsis, where we know that the longer the wait the worse the damage.

"The ambulance service have protocols in place in terms of being able to give antibiotics and IV fluids, but it's not quite the same.

"What a patient with sepsis needs is actually really intensive emergency medicine and critical care. That's not the sort of thing you can deliver in the back of an ambulance."

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Colin Graham, chief operating officer at Sepsis Research FEAT, called for more accurate recording of sepsis figures amid fears that too many cases are missed and under-counted.

He said: "Since our first joint campaign, Scottish Government figures note that there are 4,000 deaths from sepsis in Scotland every year.

"However, we believe this figure is understated and actual figures for sepsis in Scotland, and indeed in the wider UK, are probably much higher than reported.

"While we understand the difficulties of collecting statistics due to sepsis often masquerading as other illnesses, we would encourage the Government and the NHS to regularly report the true figures regarding sepsis."